Thymidine deacylation

Condensation of LXVIa (R = p-toluyl) with monomercurithymine (prepared from 1-acetylthymine) produces a mixture of acylated nucleoside anomers (LXVlb and LXVIc, R = thyminyl) which are separated and de-esterified to thymidine and a-thymidine. Similarly, reaction of N-acetylcytosinemercury (LV) with LXVIa (R = p-chlorobenzoyl) yields the a and ft anomers of acylated 2-deoxycytidine which, after separation and deacylation, are converted smoothly to 2-deoxycytidine (LXVlb, R = H, R = cytosinyl) and its a anomer (LXVIc). In like manner, 2-deoxy-5 -fluoro-uridine and -cytidine were synthesized, along with their... 

Fig. (22). Antigen-Specific Spleen Cell Proliferation Following Immunization with Ovalbumin. Mice (S/group) were either untreated (negative control) or immunized subcutaneously with ovalbumin (OVA 2 injections 2 weeks apart) plus PBS (no adjuvant control) or the indicated adjuvants [200 pg alum, 10 pg quillaja saponin, 250, 50, or 10 pg deacylated quillaja saponin (DS. Q, saponin), and 250, 50, or 10 pg GPI-OlOO]. Spleen cells were harvested 1 week after the 2" immunization and incubated at 37 C in 5% CO2 for 3 days to measure the proliferative response (by H-thymidine incorporation in counts per minute, or cpm) in response to medium (background) or 10 pg OVA. The data shown for each group represent the means (antigen response minus background response) of T lymphocyte proliferative response.

Tetrahydrofuranyl ethers of thymidine and 2 -deoxycytidine have been prepared by acid-catalysed reaction of the nucleosides with 2,3 dihydrofuran mixtures of the 3 - and 5 -mono- and 3 5 -di-ethers were obtained. 3 -0-Tetra-hydrofuranyl-thymidine was also obtained by etherification of 5 -6>-palmitoyl thymidine followed by deacylation, and rat liver microsomes were found to convert the 3, 5 -diether selectively to the 5 -ether. The puramycin analogues (58) has been prepared from a 5 -blocked adenosine derivative. 

Trl-O-benzoyl- and Q-acetyl-thymidine and uridine can be deacylated by KCN in MeOH.159... 

Further approaches to AZT have been reported. The anhydronucleoside (74) was obtained directly from thymidine by two sequential Mitsunobu reactions, and, after treatment with LlNb and deacylation, gave AZT in 73% overall yield.86 The same group has also used D-xylose to prepare AZT, by condensation of l,2-di-0-acetyl-3,5-di-(7-benzyl-D-xylofuranose with silylated thymine, and deoxygenation at C-2 to give a known intermediate for AZT. 87 In an approach from acyclic precursors, the Sharpless epoxidation product (75) was manipulated as indicated in Scheme 11 the stereospecificity in the cyclization, which gave only the p-anomer, was rationalized... 

Interest continues in the use of enzymes fcH- selective acylation and deacylation of nucleosides (see last three Vrdumes). Using oxime esters as acyl drmors, the lipase from Candida antarctica forms esters at 0-5 of libonucleosides and deoxyribonucleosides with good regioselectivity, and the same selectivity was found with the same enzyme in the butanoylation of a-thymidine, xy/o-thymidine, arabinofuranosyl nucleosides, and 2,2 -anhydiouridine.2 3 Chemo-en matic routes to 2 -deoxynucleoside urethanes are indicated in Scheme 14.724 when... 

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